Effect of metformin treatment on brain 18F-FDG uptake: a translational study

Introduction Metformin is one of the most widely used drugs to control diabetes type 2. However, there is no indication of pausing metformin treatment before an 18 F-FDG PET scan. The aim of this study is to evaluate if metformin, in both patients and mice, can alter brain 18 F-FDG uptake. Methods In vivo 18 F-FDG PET scans were carried out in male mice. Animals were treated with saline or metformin (300 mg/kg) 10 min before 18 F-FDG or chronically (3 weeks) in drinking water. Separately, patients with non-pathological 18 F-FDG brain scans were distributed into two groups: metformin-treated ( n = 12) and control patients ( n = 27). PET images were structurally normalized to brain templates, corrected to whole-brain activity, and compared using SPM12. Results In mice, acute treatment induced a significant hypermetabolism in several brain regions including hippocampus (1.07 ± 0.07 vs 0.94 ± 0.08; p = 0.0002) and thalamus (1.17 ± 0.08 vs 1.00 ± 0.08; p = 0.0002). Chronic treatment increased tracer uptake only in cortical regions. Similarly, treated patients showed hypermetabolism in the temporal lobe (1.03 ± 0.04 vs 0.97 ± 0.04; p < 0.0001) and white matter and lower uptake in frontal cortical regions (1.24 ± 0.04 vs 1.28 ± 0.06; p = 0.0165). Linear regression to HbA1c showed a negative correlation to 18 F-FDG uptake in frontal and parietal cortical subregions, but no correlation to temporal lobe uptake. Discussion Our results show that metformin treatment might modify 18 F-FDG uptake in temporal lobe structures. On the other hand, lower uptake in frontal cortex might be attributable to the diabetic condition. Thus, new studies modifying the treatment regimen in diabetic patients prior to performing an 18 F-FDG PET are warranted.